Remdesivir Resistance in Transplant Recipients With Persistent Coronavirus Disease 2019.

New mutations conferring resistance to SARS-CoV-2 therapeutics have important clinical implications. We describe the first cases of an independently acquired V792I RNA-dependent RNA polymerase mutation developing in renal transplant recipients after remdesivir exposure. Our work underscores the need for augmented efforts to identify concerning mutations and address their clinical implications.

Inflammatory and Infectious Syndromes Associated With Cancer Immunotherapies.

Immunotherapy using antibodies to immune checkpoint molecules or targeted chimeric antigen receptor-modified T cells (CAR-T cells) represent dramatic advances in cancer treatment. These therapies mediate immune-related adverse events that may mimic or amplify infectious presentations. Checkpoint inhibitor therapy may be associated with diverse irAEs including mild skin, endocrine, and autoimmune manifestations or severe inflammatory processes including colitis, pneumonitis, myocarditis, and shock. CAR-T-cell therapies may induce toxicities including cytokine-release syndrome with fevers and multiorgan dysfunction, CAR-T-cell-related encephalopathy syndrome with altered mental status and neurologic dysfunction, or hemophagocytic lymphohistiocytosis-macrophage-activation syndrome. Infectious risks may relate to prior cancer therapies or to treatments of inflammatory dysregulation, including corticosteroids and inhibitors of tumor necrosis factor-α and interleukin-6. Immune activation may unmask subclinical infections. Clinical approaches must attempt to identify infections in the face of immunotherapy-associated inflammatory processes. Empirical antimicrobial therapies should not be delayed based on the presumption of noninfectious syndromes.

Late polymicrobial transjugular intrahepatic portosystemic shunt infection in a liver transplant patient: A case report.

BACKGROUND: Infection of a transjugular intrahepatic portosystemic shunt (TIPS) stent is a rare and serious complication that most commonly occurs during TIPS creation and revision. Patients typically present with recurrent bacteremia due to shunt occlusion or vegetation. To date there are approximately 58 cases reported. We present a patient diagnosed with late polymicrobial TIPS infection five years following TIPS creation. CASE SUMMARY: A 63-year-old female status-post liver transplant with recurrent cirrhosis and portal hypertension presented with sepsis and recurrent extended-spectrum beta-lactamase Escherichia coli bacteremia. Computed tomography of the abdomen revealed an occluded TIPS with thrombus extension into the distal right portal vein, and focal thickening of the cecum and ascending colon. Colonoscopy revealed patchy ulcers in these areas with histopathology demonstrating ulcerated colonic mucosa with fibrinopurulent exudate. Shunt thrombectomy and revision revealed infected-appearing thrombus. Patient initially cleared her infection with antibacterial therapy and TIPS revision; however, soon after, she developed Enterobacter cloacae bacteremia and Candida glabrata and C. albicans fungemia with recurrent TIPS thrombosis. She remained on antifungal therapy indefinitely and later developed vancomycin-resistant Enterococcus faecium with recurrent TIPS thrombosis. The option of liver re-transplant for removal of the infected TIPS was not offered given her critical illness and complex shunt anatomy. The patient became intolerant to linezolid and elected hospice care. CONCLUSION: Clinicians should be aware that TIPS superinfection may occur as long as five years following TIPS creation in an immunocompromised patient.

Remdesivir resistance in transplant recipients with persistent COVID-19.

The medical community currently lacks robust data regarding the incidence, prevalence, and clinical significance of mutations associated with resistance to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) therapeutics. This report describes two renal transplant recipients who, after remdesivir exposure, developed a de novo V792I RNA-dependent RNA polymerase (RdRp) mutation that has recently been found to confer resistance to remdesivir in vitro . To the best of our knowledge, this publication is the first to document the emergence of V792I in patients treated with remdesivir. Our work underscores the critical need for augmented efforts to identify concerning mutations and address their clinical implications.

A Call for Caution in the Immunocompromised: Coronavirus Disease 2019 Associated With Mortality in a Vaccinated Lung Transplant Recipient.

We describe a vaccinated lung transplant recipient who experienced a fatal outcome associated with coronavirus disease 2019 (COVID-19). Tocilizumab was administered. The patient exhibited clinical and radiographic evidence of colitis during the course of multiple secondary infections. This report emphasizes the need for more conservative precautions to prevent COVID-19 infection in transplant recipients.

Mycobacterial Musculoskeletal Infections.

Although less common as causes of musculoskeletal infection than pyogenic bacteria, both Mycobacterium tuberculosis and nontuberculous mycobacteria can infect bones and joints. Although tuberculous arthritis and osteomyelitis have been recognized for millennia, infections caused by nontuberculous mycobacteria are being identified more often, likely because of a more susceptible host population and improvements in diagnostic capabilities. Despite advances in modern medicine, mycobacterial infections of the musculoskeletal system remain particularly challenging to diagnose and manage. This article discusses clinical manifestations of musculoskeletal infections caused by Mycobacterium tuberculosis and nontuberculous mycobacteria. Pathogenesis, unique risk factors, and diagnostic and therapeutic approaches are reviewed.

Mycobacterial Musculoskeletal Infections.

Although less common as causes of musculoskeletal infection than pyogenic bacteria, both Mycobacterium tuberculosis and nontuberculous mycobacteria can infect bones and joints. Although tuberculous arthritis and osteomyelitis have been recognized for millennia, infections caused by nontuberculous mycobacteria are being identified more often, likely because of a more susceptible host population and improvements in diagnostic capabilities. Despite advances in modern medicine, mycobacterial infections of the musculoskeletal system remain particularly challenging to diagnose and manage. This article discusses clinical manifestations of musculoskeletal infections caused by Mycobacterium tuberculosis and nontuberculous mycobacteria. Pathogenesis, unique risk factors, and diagnostic and therapeutic approaches are reviewed.